Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.

MOREL GR; SOSA YE; BELLINI MJ; CARRI NG; RODRIGUEZ SS; BOHN MC; GOYA RG

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2010 vol. 167 p. 946 - 953

0306-4522

Abstract?Progressive dysfunction of hypothalamic tuberoinfundibulardopaminergic (TIDA) neurons during normalaging is associated in the female rat with chronic hyperprolactinemia.We assessed the effectiveness of glial cellline-derived neurotrophic factor (GDNF) gene therapy to restoreTIDA neuron function in senile female rats and reversetheir chronic hyperprolactinemia. Young (2.5 months) andsenile (29 months) rats received a bilateral intrahypothalamicinjection (1010 pfu) of either an adenoviral vector expressingthe gene for -galactosidase; (Y-gal and S-gal, respectively)or a vector expressing rat GDNF (Y-GDNF and S-GDNF,respectively). Transgenic GDNF levels in supernatants ofGDNF adenovector-transduced N2a neuronal cell cultureswere 254 ng/ml, as determined by bioassay. In the rats,serum prolactin (PRL) was measured at regular intervals. Onday 17 animals were sacrificed and neuronal nuclear antigen(NeuN) and tyrosine hydroxylase (TH) immunoreactive cellscounted in the arcuate?periventricular hypothalamic region.The S-GDNF but not the S-gal rats, showed a significantreduction in body weight. The chronic hyperprolactinemia ofthe senile females was significantly ameliorated in the SGDNFrats (P